Figure 6.

Five phases in the development of intracellular Aβ42(E22G) aggregates. The aggregation of Aβ42 Arctic mutant initiates from oligomerization of monomers, which then rapidly assemble to form fibrils. Multiple fibrils connect with high affinity to form bundles, clusters, and eventually aggresomes. The five phases in the structural progression of Arctic mutant aggregates are shown from left to right. Phase 1, soluble oligomers in cytosol. Phase 2, linear fibrils ranging from 500 nm to 2 μm in length, representing amyloid building blocks and the most universal form of intracellular aggregates. Phase 3, fibril bundles consisting of multiple fibrils aligned in a similar orientation. Phase 4, multiple fibrils assembled as a tightly bound cluster. Phase 5, a large number of fibrillary fragments that form highly compacted aggresomes, which are resistant to degradation.